This invention generally pertains to heterocyclic carbon compounds having drug and bio-affecting properties and to their preparation and use. In particular, the invention is concerned with 1,4-disubstituted piperazine derivatives wherein one substituent is a substituted pyridin-2-yl ring, generally with a substituent in the 3-position of the ring; and the other is a butylene chain bearing a cyclic imide ring moiety at its terminus. Examples of these cyclic imide heterocycles are depicted below: ##STR1##
A considerable amount of related art has accumulated over the past 10 years. The more pertinent related art may be viewed in light of the following general structural formula (1) ##STR2## in which alk is an alkylene chain connecting the piperazine ring and the cyclic imide group and B is a heterocyclic ring with optional substituents.
Wu, et al, U.S. Pat. Nos. 3,717,634, 3,907,801 and a corresponding Wu, et al, publication--J. Med. Chem., 15, 447-479 (1972)--describe various azaspiro[4.5]decanedione psychotropic compounds wherein B represents various heterocycles such as pyridine, pyrimidine, or triazine, all with optional substituents. Specifically B can be, inter alia, ##STR3## wherein one of W and Y is CH and the other is nitrogen; R.sup.1 and R.sup.2 are independently selected from hydrogen, lower (C.sub.1 -C.sub.6) alkyl or lower alkoxy. As can be seen, B cannot be a 3-substituted pyridin-2-yl moiety, as in the instant invention.
Temple, et al, in U.S. Pat. No. 4,305,944 discloses azaspiro[4.5]decanedione tranquilizing compounds wherein B is a 3-cyanopyridin-2-yl or 3-methoxypyridin-2-yl moiety; and in U.S. Pat. No. 4,361,565 they disclose dialkylglutarimide compounds wherein B is a 3-cyanopyridin-2-yl ring, either unsubstituted or with halogen or trifluoromethyl as a second substituent on the pyridine ring.
Temple and Yeager in U.S. Pat. Nos. 4,367,335 and 4,456,756 disclose thiazolidinediones and spirothiazolidinediones wherein B is a 2-pyridine radical, either unsubstituted or containing a cyano substituent.
A preferred compound of this series is known as MJ 13980, formula (2), ##STR4## but was found to have toxicological problems prior to clinical testing. Specifically, adrenal hypertrophic changes were associated with chronic administration of MJ 13980. Examination of the molecular structure of MJ 13980 suggests that the cyanopyridine moiety is a likely suspect as the pharmacophore which may be responsible for the unwanted toxicological effect.
While the psychotropic compounds listed above are generally related to the compounds of the instant invention, they are nonetheless distinguishable therefrom on both specific structural as well as pharmacological grounds. Essentially, in the art compounds, B is either unsubstituted or bears a cyano group usually in the 3-position. This differs from the present compounds which have no cyano group and are generally substituted in the 3-position.